JP2021531279A - 自然リンパ系細胞による小膠細胞活性化の抑制 - Google Patents
自然リンパ系細胞による小膠細胞活性化の抑制 Download PDFInfo
- Publication number
- JP2021531279A JP2021531279A JP2021502605A JP2021502605A JP2021531279A JP 2021531279 A JP2021531279 A JP 2021531279A JP 2021502605 A JP2021502605 A JP 2021502605A JP 2021502605 A JP2021502605 A JP 2021502605A JP 2021531279 A JP2021531279 A JP 2021531279A
- Authority
- JP
- Japan
- Prior art keywords
- ilc2
- subject
- activated
- cells
- microglial activation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000006724 microglial activation Effects 0.000 title claims abstract description 77
- 210000004698 lymphocyte Anatomy 0.000 title claims description 58
- 230000001629 suppression Effects 0.000 title description 26
- 238000000034 method Methods 0.000 claims abstract description 169
- 230000008499 blood brain barrier function Effects 0.000 claims abstract description 75
- 210000001218 blood-brain barrier Anatomy 0.000 claims abstract description 75
- 230000035699 permeability Effects 0.000 claims abstract description 34
- 210000004964 innate lymphoid cell Anatomy 0.000 claims description 428
- 210000004027 cell Anatomy 0.000 claims description 110
- 102000017761 Interleukin-33 Human genes 0.000 claims description 86
- 108010067003 Interleukin-33 Proteins 0.000 claims description 86
- 230000001965 increasing effect Effects 0.000 claims description 82
- 239000008194 pharmaceutical composition Substances 0.000 claims description 76
- 239000003795 chemical substances by application Substances 0.000 claims description 70
- 210000002418 meninge Anatomy 0.000 claims description 64
- 230000002829 reductive effect Effects 0.000 claims description 58
- 102000004127 Cytokines Human genes 0.000 claims description 47
- 108090000695 Cytokines Proteins 0.000 claims description 47
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 claims description 46
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 claims description 46
- 238000004519 manufacturing process Methods 0.000 claims description 46
- 108010002350 Interleukin-2 Proteins 0.000 claims description 40
- 102000000588 Interleukin-2 Human genes 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 36
- 108010002586 Interleukin-7 Proteins 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 32
- 101150077804 TIMP1 gene Proteins 0.000 claims description 31
- 102000005353 Tissue Inhibitor of Metalloproteinase-1 Human genes 0.000 claims description 31
- 229940079593 drug Drugs 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 239000003937 drug carrier Substances 0.000 claims description 26
- 208000035475 disorder Diseases 0.000 claims description 15
- 230000031261 interleukin-10 production Effects 0.000 claims description 15
- 230000002992 thymic effect Effects 0.000 claims description 14
- 101100369802 Caenorhabditis elegans tim-1 gene Proteins 0.000 claims description 13
- 108090000978 Interleukin-4 Proteins 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 230000009826 neoplastic cell growth Effects 0.000 claims description 13
- 230000004770 neurodegeneration Effects 0.000 claims description 13
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 206010012289 Dementia Diseases 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 102100031789 Myeloid-derived growth factor Human genes 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 208000024777 Prion disease Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 230000003557 neuropsychological effect Effects 0.000 claims description 6
- 208000020431 spinal cord injury Diseases 0.000 claims description 6
- 208000035143 Bacterial infection Diseases 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 5
- 201000009906 Meningitis Diseases 0.000 claims description 5
- 208000003435 Optic Neuritis Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 208000036142 Viral infection Diseases 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 5
- 208000028683 bipolar I disease Diseases 0.000 claims description 5
- 208000025307 bipolar depression Diseases 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 230000003612 virological effect Effects 0.000 claims description 5
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 230000009529 traumatic brain injury Effects 0.000 claims description 4
- 239000000203 mixture Substances 0.000 abstract description 37
- 241000699670 Mus sp. Species 0.000 description 106
- 101100193633 Danio rerio rag2 gene Proteins 0.000 description 70
- 101100193635 Mus musculus Rag2 gene Proteins 0.000 description 70
- 210000000274 microglia Anatomy 0.000 description 50
- 230000002025 microglial effect Effects 0.000 description 50
- 239000006228 supernatant Substances 0.000 description 42
- 238000002474 experimental method Methods 0.000 description 39
- 210000004556 brain Anatomy 0.000 description 37
- 230000002950 deficient Effects 0.000 description 37
- 230000004913 activation Effects 0.000 description 36
- 230000020411 cell activation Effects 0.000 description 29
- 230000014509 gene expression Effects 0.000 description 28
- 210000001519 tissue Anatomy 0.000 description 27
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 26
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 26
- 101000852968 Homo sapiens Interleukin-1 receptor-like 1 Proteins 0.000 description 23
- 101000585365 Homo sapiens Sulfotransferase 2A1 Proteins 0.000 description 22
- 102100029867 Sulfotransferase 2A1 Human genes 0.000 description 22
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 21
- 108090000176 Interleukin-13 Proteins 0.000 description 20
- 102000003816 Interleukin-13 Human genes 0.000 description 20
- 210000001744 T-lymphocyte Anatomy 0.000 description 20
- 239000002953 phosphate buffered saline Substances 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 18
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 18
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 18
- 230000003959 neuroinflammation Effects 0.000 description 18
- 230000004044 response Effects 0.000 description 18
- 210000003169 central nervous system Anatomy 0.000 description 17
- 108010002616 Interleukin-5 Proteins 0.000 description 15
- 102000000743 Interleukin-5 Human genes 0.000 description 15
- 201000002491 encephalomyelitis Diseases 0.000 description 15
- 238000006386 neutralization reaction Methods 0.000 description 14
- 238000012546 transfer Methods 0.000 description 14
- 238000000540 analysis of variance Methods 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 230000006775 microglial inflammation Effects 0.000 description 13
- 230000003248 secreting effect Effects 0.000 description 13
- 102000004388 Interleukin-4 Human genes 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 230000008595 infiltration Effects 0.000 description 12
- 238000001764 infiltration Methods 0.000 description 12
- 229940028885 interleukin-4 Drugs 0.000 description 12
- 102400001107 Secretory component Human genes 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 101150084229 ATXN1 gene Proteins 0.000 description 10
- 108010012236 Chemokines Proteins 0.000 description 10
- 102000019034 Chemokines Human genes 0.000 description 10
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 10
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 10
- -1 IL-10 Proteins 0.000 description 10
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 10
- 101001043810 Macaca fascicularis Interleukin-7 receptor subunit alpha Proteins 0.000 description 10
- 101150035730 Mmp9 gene Proteins 0.000 description 10
- 101001065566 Mus musculus Lymphocyte antigen 6A-2/6E-1 Proteins 0.000 description 10
- 230000001419 dependent effect Effects 0.000 description 10
- 238000002372 labelling Methods 0.000 description 10
- 210000004072 lung Anatomy 0.000 description 10
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 9
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 8
- 101150085950 IL10 gene Proteins 0.000 description 8
- 230000004888 barrier function Effects 0.000 description 8
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 230000002093 peripheral effect Effects 0.000 description 8
- 101000819111 Homo sapiens Trans-acting T-cell-specific transcription factor GATA-3 Proteins 0.000 description 7
- 102100021386 Trans-acting T-cell-specific transcription factor GATA-3 Human genes 0.000 description 7
- 108091023040 Transcription factor Proteins 0.000 description 7
- 102000040945 Transcription factor Human genes 0.000 description 7
- 230000005856 abnormality Effects 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 210000001616 monocyte Anatomy 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000002269 spontaneous effect Effects 0.000 description 7
- 108010002335 Interleukin-9 Proteins 0.000 description 6
- 102000000585 Interleukin-9 Human genes 0.000 description 6
- 238000012258 culturing Methods 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 238000003559 RNA-seq method Methods 0.000 description 5
- 238000000692 Student's t-test Methods 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 229960003699 evans blue Drugs 0.000 description 5
- 210000004700 fetal blood Anatomy 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000003472 neutralizing effect Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 210000000130 stem cell Anatomy 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 4
- 210000001642 activated microglia Anatomy 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 210000004324 lymphatic system Anatomy 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 3
- 102100022338 Integrin alpha-M Human genes 0.000 description 3
- 102100021457 Killer cell lectin-like receptor subfamily G member 1 Human genes 0.000 description 3
- 101100013967 Mus musculus Gata3 gene Proteins 0.000 description 3
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 3
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 230000003044 adaptive effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000005098 blood-cerebrospinal fluid barrier Anatomy 0.000 description 3
- 239000001045 blue dye Substances 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FBFJOZZTIXSPPR-UHFFFAOYSA-N 1-(4-aminobutyl)-2-(ethoxymethyl)imidazo[4,5-c]quinolin-4-amine Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CCCCN)C3=C(N)N=C21 FBFJOZZTIXSPPR-UHFFFAOYSA-N 0.000 description 2
- 101150053137 AIF1 gene Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102100029855 Caspase-3 Human genes 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 208000019028 Epidermal thickening Diseases 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000971533 Homo sapiens Killer cell lectin-like receptor subfamily G member 1 Proteins 0.000 description 2
- 206010020649 Hyperkeratosis Diseases 0.000 description 2
- 101150019209 IL13 gene Proteins 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 239000008156 Ringer's lactate solution Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229940124613 TLR 7/8 agonist Drugs 0.000 description 2
- 210000004241 Th2 cell Anatomy 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000004721 adaptive immunity Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 239000000367 immunologic factor Substances 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000007570 microbleeding Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 230000002314 neuroinflammatory effect Effects 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 230000007918 pathogenicity Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 230000001185 psoriatic effect Effects 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000005737 synergistic response Effects 0.000 description 2
- 210000002303 tibia Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- GITVQUOQRHRGQQ-UHFFFAOYSA-N 1-(4-amino-2-butylimidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol Chemical compound C1=CC=CC2=C(N(C(CCCC)=N3)CC(C)(C)O)C3=C(N)N=C21 GITVQUOQRHRGQQ-UHFFFAOYSA-N 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 210000003967 CLP Anatomy 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920004934 Dacron® Polymers 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010064212 Eosinophilic oesophagitis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 1
- 108010076288 Formyl peptide receptors Proteins 0.000 description 1
- 102000011652 Formyl peptide receptors Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010034791 Heterochromatin Proteins 0.000 description 1
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 1
- 101001078133 Homo sapiens Integrin alpha-2 Proteins 0.000 description 1
- 101000590691 Homo sapiens MAGUK p55 subfamily member 2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102100025305 Integrin alpha-2 Human genes 0.000 description 1
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 1
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 101710150988 Killer cell lectin-like receptor subfamily G member 1 Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 101710122625 Low affinity immunoglobulin gamma Fc region receptor II Proteins 0.000 description 1
- 206010025280 Lymphocytosis Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 101150106019 Mmp2 gene Proteins 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 101100153331 Mus musculus Timp1 gene Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 108091008778 RORγ2 Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000006470 autoimmune attack Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 208000025698 brain inflammatory disease Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000033026 cell fate determination Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 210000002987 choroid plexus Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 101150047356 dec-1 gene Proteins 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000001712 encephalitogenic effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 201000000708 eosinophilic esophagitis Diseases 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 210000004458 heterochromatin Anatomy 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000004047 hyperresponsiveness Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 231100000859 kill neurons Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000001703 neuroimmune Effects 0.000 description 1
- 230000003962 neuroinflammatory response Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 101150023701 nfil3 gene Proteins 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 210000003446 pia mater Anatomy 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 238000009580 stem-cell therapy Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- CCEKAJIANROZEO-UHFFFAOYSA-N sulfluramid Chemical group CCNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F CCEKAJIANROZEO-UHFFFAOYSA-N 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000002287 time-lapse microscopy Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46432—Nervous system antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46433—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Developmental Biology & Embryology (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862698545P | 2018-07-16 | 2018-07-16 | |
| US62/698,545 | 2018-07-16 | ||
| PCT/IB2019/055354 WO2020016684A1 (en) | 2018-07-16 | 2019-06-25 | Suppression of microglial activation with innate lymphoid cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2021531279A true JP2021531279A (ja) | 2021-11-18 |
Family
ID=67874483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021502605A Pending JP2021531279A (ja) | 2018-07-16 | 2019-06-25 | 自然リンパ系細胞による小膠細胞活性化の抑制 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20200016205A1 (ko) |
| EP (1) | EP3823637A1 (ko) |
| JP (1) | JP2021531279A (ko) |
| KR (1) | KR20210033012A (ko) |
| CN (1) | CN112805017A (ko) |
| AU (1) | AU2019304186A1 (ko) |
| BR (1) | BR112021000214A2 (ko) |
| CA (1) | CA3106599A1 (ko) |
| IL (1) | IL280012A (ko) |
| MX (1) | MX2021000639A (ko) |
| WO (1) | WO2020016684A1 (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116370608B (zh) * | 2023-05-15 | 2024-04-12 | 华中科技大学 | Il-33在长期抑郁引起的记忆损伤治疗中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015042521A1 (en) * | 2013-09-20 | 2015-03-26 | University Of Virginia Patent Foundation | Compositions and methods for treatment of autoimmune and inflammatory diseases and disorders |
| US20170360907A1 (en) * | 2014-12-04 | 2017-12-21 | The University Of North Carolina At Chapel Hill | Compositions and methods for preventing and treating graft versus host disease |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7205280B2 (en) | 1998-03-11 | 2007-04-17 | Cognosci, Inc. | Methods of suppressing microglial activation |
| AU2997099A (en) | 1998-03-11 | 1999-09-27 | Duke University | Methods of suppressing microglial activation |
| WO2011106476A1 (en) | 2010-02-25 | 2011-09-01 | Abt Holding Company | Modulation of microglia activation |
| US20120237482A1 (en) | 2011-03-18 | 2012-09-20 | Juan Rodriguez | Methods for treatment of neurological disorders by modulation of microglial activation |
| US20190000754A1 (en) * | 2015-10-05 | 2019-01-03 | Seinda Biomedical Corporation | Therapeutic compositions for the treatment of dry eye and related ocular surface diseases |
| KR20190086764A (ko) * | 2016-11-30 | 2019-07-23 | 앵스티띠 파스퇴르 | 사람 선천성 림프 세포 전구체: 확인, 특성화, 적용 |
-
2019
- 2019-06-25 EP EP19765318.1A patent/EP3823637A1/en active Pending
- 2019-06-25 BR BR112021000214-6A patent/BR112021000214A2/pt unknown
- 2019-06-25 WO PCT/IB2019/055354 patent/WO2020016684A1/en unknown
- 2019-06-25 KR KR1020217004401A patent/KR20210033012A/ko unknown
- 2019-06-25 US US16/451,426 patent/US20200016205A1/en not_active Abandoned
- 2019-06-25 JP JP2021502605A patent/JP2021531279A/ja active Pending
- 2019-06-25 AU AU2019304186A patent/AU2019304186A1/en active Pending
- 2019-06-25 MX MX2021000639A patent/MX2021000639A/es unknown
- 2019-06-25 CN CN201980047602.3A patent/CN112805017A/zh active Pending
- 2019-06-25 CA CA3106599A patent/CA3106599A1/en active Pending
-
2021
- 2021-01-07 IL IL280012A patent/IL280012A/en unknown
-
2023
- 2023-04-27 US US18/140,344 patent/US20230285459A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015042521A1 (en) * | 2013-09-20 | 2015-03-26 | University Of Virginia Patent Foundation | Compositions and methods for treatment of autoimmune and inflammatory diseases and disorders |
| US20170360907A1 (en) * | 2014-12-04 | 2017-12-21 | The University Of North Carolina At Chapel Hill | Compositions and methods for preventing and treating graft versus host disease |
Non-Patent Citations (1)
| Title |
|---|
| BROWN, MA., ET AL.: "Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disea", FRONTIERS IN IMMUNOLOGY, vol. 9, no. 514, JPN6023017779, 21 March 2018 (2018-03-21), pages 1 - 14, ISSN: 0005049609 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112805017A (zh) | 2021-05-14 |
| CA3106599A1 (en) | 2020-01-23 |
| US20200016205A1 (en) | 2020-01-16 |
| AU2019304186A1 (en) | 2021-02-04 |
| US20230285459A1 (en) | 2023-09-14 |
| WO2020016684A1 (en) | 2020-01-23 |
| IL280012A (en) | 2021-03-01 |
| KR20210033012A (ko) | 2021-03-25 |
| MX2021000639A (es) | 2021-03-25 |
| EP3823637A1 (en) | 2021-05-26 |
| BR112021000214A2 (pt) | 2021-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105008521B (zh) | 调节干细胞的免疫调节作用的方法 | |
| US20190276803A1 (en) | Method of culturing immune cells, kit for thereof, immune cell cultured medium obtained by same method, cosmetic composition and pharmaceutical composition comprising thereof | |
| Bazzoni et al. | Extracellular vesicle-dependent communication between mesenchymal stromal cells and immune effector cells | |
| JP2022169781A (ja) | 治療用のプールされた血液アポトーシス細胞調製物及びそれらの使用 | |
| WO2021174738A1 (zh) | 表面pd-l1分子过表达的间充质干细胞膜包被的仿生纳米颗粒及其制备和应用 | |
| US11471517B2 (en) | Compositions and methods for preventing and treating graft versus host disease | |
| US20190060367A1 (en) | 3-d collagen scaffold-generated exosomes and uses thereof | |
| US20120100108A1 (en) | Compositions and methods of treating no-option critical limb ischemia (cli) | |
| JP7235259B2 (ja) | Ｇｖｈｄ又は腫瘍を治療するための骨髄系由来サプレッサー細胞のインフラマソーム活性化の調節 | |
| Wang et al. | Acetyl-11-keto-β-boswellic acid inhibits the secretion of cytokines by dendritic cells via the TLR7/8 pathway in an imiquimod-induced psoriasis mouse model and in vitro | |
| Pischiutta et al. | Mesenchymal stromal cell secretome for traumatic brain injury: Focus on immunomodulatory action | |
| KR102100307B1 (ko) | 인간 림프 기관-유래 억제성 기질 세포의 분리 및 용도 | |
| US20230285459A1 (en) | Suppression of Microglial Activation with Innate Lymphoid Cells | |
| WO2024070382A1 (ja) | 微小粒子、ｎｋ細胞活性化剤、ｎｋ細胞の培養方法、活性化ｎｋ細胞の製造方法およびｎｋ細胞の活性化方法 | |
| US20220175842A1 (en) | Exosomes and uses thereof in diseases of the brain | |
| WO2014089397A1 (en) | Compositions and methods of treating and preventing pulmonary fibrosis | |
| WO2018013971A1 (en) | Methods of reducing chronic graft-versus-host disease | |
| JP2024512001A (ja) | 腫瘍低酸素教育済み再生マクロファージを得る方法、及びその、再生医療における使用 | |
| Ghita | Adipose derived stromal vascular fraction: therapeutic potential of renal artery administration in renal ischaemia reperfusion injury | |
| KR20230087351A (ko) | 전분화능 줄기세포 기반 혈관성 인지장애 및 치매 예방 또는 치료용 조성물 | |
| Pulido | The role of Batf3-dependent dendritic cells and the IL-23 receptor in atherosclerosis | |
| Gil Pulido | The role of Batf3-dependent dendritic cells and the IL-23 receptor in atherosclerosis | |
| White | Characterisation of microglia's inflammatory response and investigation of the effect of mesenchymal stem cells-conditioned media | |
| Cohen | Unresolved inflammation following spinal cord injury-causes and effects on the central nervous system | |
| Longbrake | Consequences of differential macrophage activation after spinal cord trauma |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220624 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230427 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230502 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230802 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230929 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240109 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240408 |